Center for Epigenetics and Metabolism, INSERM U1233, Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Integrative Physiology, University of Copenhagen, Copenhagen, Denmark.
Cell Metab. 2019 Jul 2;30(1):92-110.e4. doi: 10.1016/j.cmet.2019.03.013. Epub 2019 Apr 18.
While the timing of food intake is important, it is unclear whether the effects of exercise on energy metabolism are restricted to unique time windows. As circadian regulation is key to controlling metabolism, understanding the impact of exercise performed at different times of the day is relevant for physiology and homeostasis. Using high-throughput transcriptomic and metabolomic approaches, we identify distinct responses of metabolic oscillations that characterize exercise in either the early rest phase or the early active phase in mice. Notably, glycolytic activation is specific to exercise at the active phase. At the molecular level, HIF1α, a central regulator of glycolysis during hypoxia, is selectively activated in a time-dependent manner upon exercise, resulting in carbohydrate exhaustion, usage of alternative energy sources, and adaptation of systemic energy expenditure. Our findings demonstrate that the time of day is a critical factor to amplify the beneficial impact of exercise on both metabolic pathways within skeletal muscle and systemic energy homeostasis.
尽管进食时间很重要，但运动对能量代谢的影响是否仅限于特定的时间窗口尚不清楚。由于昼夜节律调节是控制代谢的关键，因此了解一天中不同时间进行的运动的影响与生理学和体内平衡有关。使用高通量转录组学和代谢组学方法，我们确定了代谢波动的不同反应，这些反应以小鼠在早期休息阶段或早期活动阶段进行运动为特征。值得注意的是，糖酵解的激活是运动在活动阶段特有的。在分子水平上，HIF1α 是缺氧时糖酵解的核心调节剂，在运动时会以时间依赖性的方式被选择性激活，导致碳水化合物耗尽、使用替代能源以及适应全身能量消耗。我们的研究结果表明，时间是一个关键因素，可以增强运动对骨骼肌和全身能量平衡中代谢途径的有益影响。
